For Intravenous Injection Only

In ADD-Vantage® Drug Delivery System

To reduce the development of drug-resistant bacteria and maintain the effectiveness of ampicillin and other antibacterial drugs, ampicillin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Ampicillin for Injection, USP the monosodium salt of [2S-[2α,5α,6β(S*)]]-6-[(aminophenylacetyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid, is a synthetic penicillin. It is an antibacterial agent with a broad spectrum of bactericidal activity against both penicillin-susceptible Gram-positive organisms and many common Gram-negative pathogens.

Ampicillin for Injection, USP is a white to cream-tinged, crystalline powder. The reconstituted solution is clear, colorless and free from visible particulates.

Each ADD-Vantage® vial of Ampicillin for Injection, USP contains ampicillin sodium equivalent to 1 gram or 2 grams ampicillin. Ampicillin for Injection, USP contains 2.9 milliequivalents of sodium per gram of ampicillin.

It has the following molecular structure:

The molecular formula is C16H18N3NaO4S, and the molecular weight is 371.39. The pH range of the reconstituted solution is 8 to 10.

CLINICAL PHARMACOLOGY

Ampicillin for Injection, USP diffuses readily into most body tissues and fluids. However, penetration into the cerebrospinal fluid and brain occurs only when the meninges are inflamed. Ampicillin is excreted largely unchanged in the urine and its excretion can be delayed by concurrent administration of probenecid. Due to maturational changes in renal function, ampicillin half-life decreases as postmenstrual age (a sum of gestational age and postnatal age) increases for infants with postnatal age of less than 28 days. The active form appears in the bile in higher concentrations than those found in serum. Ampicillin is the least serum-bound of all the penicillins, averaging about 20% compared to approximately 60 to 90% for other penicillins. Ampicillin for Injection, USP is well tolerated by most patients and has been given in doses of 2 grams daily for many weeks without adverse reactions.

Microbiology

While in vitro studies have demonstrated the susceptibility of most strains of the following organisms, clinical efficacy for infections other than those included in the INDICATIONS AND USAGE section has not been demonstrated.

Antibacterial Activity

The following bacteria have been shown in in vitro studies to be susceptible to Ampicillin for Injection, USP:

Gram-positive Bacteria

Hemolytic and nonhemolytic streptococci

Streptococcus pneumoniae

Nonpenicillinase-producing staphylococci

Clostridium spp.

B. anthracis

Listeria monocytogenes

Most strains of enterococci.

Gram-negative Bacteria

H. influenzae

N. gonorrhoeae

N. meningitidis

Proteus mirabilis

Many strains of Salmonella, Shigella, and E. coli.

AMPICILLIN does not resist destruction by penicillinase.

Susceptibility Test Methods

Diffusion Techniques

Quantitative methods that require measurement of zone diameters provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure1,2 that has been recommended for use with disks to test the susceptibility of microorganisms to ampicillin, uses the 10 mcg ampicillin disk. Interpretation involves correlation of the diameter obtained in the disk test with the minimum inhibitory concentration (MIC) for ampicillin. Reports from the laboratory providing results of the standard single-disk susceptibility test with a 10 mcg ampicillin disk should be interpreted according to the criteria provided in Table 1.

Dilution Techniques

Quantitative methods that are used to determine minimum inhibitory concentrations (MICs) provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure1,3 uses a standardized dilution method (broth or agar) or equivalent with ampicillin powder. The MIC values obtained should be interpreted according to the criteria provided in Table 1.

Non-meningitidis S. pneumoniae isolates may be considered susceptible to ampicillin if the isolate has a penicillin MIC of ≤0.06 mcg/mL.

Susceptibility of staphylococci to ampicillin may be deduced from testing only penicillin and either cefoxitin or oxacillin.

A report of “Susceptible”(S) indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in the blood. A report of “Intermediate” (I) indicates that the result should be considered equivocal, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of the drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” (R) indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory control microorganisms1,2,3.

The 10 mcg ampicillin disk and the standard ampicillin powder should provide respectively the following zone diameters and MIC values in these laboratory test quality control strains:

INDICATIONS AND USAGE

Ampicillin for Injection, USP is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the following conditions:

Respiratory Tract Infections caused by Streptococcus pneumoniae. Staphylococcus aureus (penicillinase and nonpenicillinase-producing), H. influenzae, and Group A beta-hemolytic Streptococci.

Bacterial Meningitis caused by E. coli, Group B Streptococci, and other Gram-negative bacteria (Listeria monocytogenes, N. meningitidis). The addition of an aminoglycoside with ampicillin may increase its effectiveness against Gram-negative bacteria.

Septicemia and Endocarditis caused by susceptible Gram-positive organisms including Streptococcus spp., penicillin G-susceptible staphylococci, and enterococci. Gram-negative sepsis caused by E. coli, Proteus mirabilis and Salmonella sp. respond to ampicillin. Endocarditis due to enterococcal strains usually respond to intravenous therapy. The addition of an aminoglycoside may enhance the effectiveness of ampicillin when treating streptococcal endocarditis.

Urinary Tract Infections caused by sensitive strains of E. coli and Proteus mirabilis.

Gastrointestinal Infections caused by Salmonella typhi (typhoid fever), other Salmonella spp., and Shigella spp. (dysentery) usually respond to oral or intravenous therapy.

Bacteriology studies to determine the causative organisms and their susceptibility to ampicillin should be performed. Therapy may be instituted prior to obtaining results of susceptibility testing.

It is advisable to reserve the parenteral form of this drug for moderately severe and severe infections and for patients who are unable to take the oral forms. A change to oral ampicillin may be made as soon as appropriate.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Ampicillin for Injection, USP and other antibacterial drugs, Ampicillin for Injection, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Indicated surgical procedures should be performed.

CONTRAINDICATIONS

A history of a previous hypersensitivity reaction to any of the penicillins is a contraindication.

WARNINGS

Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens.

There have been well-documented reports of individuals with a history of penicillin hypersensitivity reactions who have experienced severe hypersensitivity reactions when treated with a cephalosporin. Before initiating therapy with a penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs, the drug should be discontinued and appropriate therapy instituted.

SERIOUS ANAPHYLACTOID REACTIONS REQUIRE IMMEDIATE EMERGENCY TREATMENT WITH EPINEPHRINE, OXYGEN, INTRAVENOUS STEROIDS, AND AIRWAY MANAGEMENT, INCLUDING INTUBATION, SHOULD ALSO BE ADMINISTERED AS INDICATED.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ampicillin for injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

PRECAUTIONS

ADVERSE REACTIONS

As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins and in those with a history of allergy, asthma, hay fever, or urticaria.

The following adverse reactions have been reported as associated with the use of ampicillin:

OVERDOSAGE

In cases of overdose, discontinue medication, treat symptomatically, and institute supportive measures as required. In patients with renal function impairment, ampicillin-class antibiotics can be removed by hemodialysis but not peritoneal dialysis.

DOSAGE AND ADMINISTRATION

The Single Use ADD-Vantage® vials are for intravenous use only. Infections of the respiratory tract and soft tissues.

Patients weighing 40 kg (88 lbs) or more: 250 mg to 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 25 to 50 mg/kg/day in equally divided doses at 6- to 8- hour intervals.

Infections of the gastrointestinal and genitourinary tracts (including those caused by Neisseria gonorrhoeae in females).

Patients weighing 40 kg (88 lbs) or more: 500 mg every 6 hours.

Patients weighing less than 40 kg (88 lbs): 50 mg/kg/day in equally divided doses at 6- to 8- hour intervals.

In the treatment of chronic urinary tract and intestinal infections, frequent bacteriological and clinical appraisal is necessary. Smaller doses than those recommended above should not be used. Higher doses should be used for stubborn or severe infections. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy.

Urethritis in males due to N. gonorrhoeae.

Adults – Two doses of 500 mg each at an interval of 8 to 12 hours. Treatment may be repeated if necessary or extended if required.

In the treatment of complications of gonorrheal urethritis, such as prostatitis and epididymitis, prolonged and intensive therapy is recommended. Cases of gonorrhea with a suspected primary lesion of syphilis should have darkfield examinations before receiving treatment. In all other cases where concomitant syphilis is suspected, monthly serological tests should be made for a minimum of four months.

The doses for the preceding infections may be given by intravenous route. A change to oral ampicillin may be made when appropriate.

DIRECTIONS FOR USE

ADD-Vantage® Vial – ampicillin for injection 1 and 2 grams.

The ADD-Vantage® vials for intravenous use only are to be used with ADD-Vantage® diluent containers: 0.9% Sodium Chloride Injection, USP, 50 mL and 100 mL, or 5% Dextrose Injection, USP, 50 mL and 100 mL.

Reconstitute ADD-Vantage® vial as directed in INSTRUCTIONS FOR USE.

Use only freshly prepared solutions. Intravenous injections should be administered immediately after reconstitution since the potency may decrease.

Summary of Utility Times for Constituted Ampicillin for Injection in the Hospira ADD-Vantage® System

INSTRUCTIONS FOR USE

To Open Diluent Container:

Peel overwrap from the corner and remove container. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

To Assemble Vial and Flexible Diluent Container:

(Use Aseptic Technique)

1.

Remove the protective covers from the top of the vial and the vial port on the diluent container as follows:
a. To remove the breakaway vial cap, swing the pull ring over the top of the vial and pull down far enough to start the opening (SEE FIGURE 1), then pull straight up to remove the cap. (SEE FIGURE 2.)
NOTE: Do not access vial with syringe.

b. To remove the vial port cover, grasp the tab on the pull ring, pull up to break the three tie strings, then pull back to remove the cover. (SEE FIGURE 3.)

2.

Screw the vial into the vial port until it will go no further. THE VIAL MUST BE SCREWED IN TIGHTLY TO ASSURE A SEAL. This occurs approximately 1/2 turn (180°) after the first audible click. (SEE FIGURE 4.) The clicking sound does not assure a seal; the vial must be turned as far as it will go. NOTE: Once vial is seated, do not attempt to remove. (SEE FIGURE4.)

3.

Recheck the vial to assure that it is tight by trying to turn it further in the direction of assembly.

4.

Label appropriately.

To Prepare Admixture:

1.

Squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial.

2.

With the other hand, push the drug vial down into the container telescoping the walls of the container. Grasp the inner cap of the vial through the walls of the container. (SEE FIGURE 5.)

3.

Pull the inner cap from the drug vial. (SEE FIGURE 6.) Verify that the rubber stopper has been pulled out, allowing the drug and diluent to mix.

4.

Mix container contents thoroughly and use within the specified time.

Preparation for Administration:

(Use Aseptic Technique)

1.

Confirm the activation and admixture of vial contents.

2.

Check for leaks by squeezing container firmly. If leaks are found, discard unit as sterility may be impaired.

3.

Close flow control clamp of administration set.

4.

Remove cover from outlet port at bottom of container.

5.

Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated.
NOTE: See full directions on administration set carton.

6.

Lift the free end of the hanger loop on the bottom of the vial, breaking the two tie strings. Bend the loop outward to lock it in the upright position, then suspend container from hanger.

7.

Squeeze and release drip chamber to establish proper fluid level in chamber.

8.

Open flow control clamp and clear air from set. Close clamp.

9.

Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.

10.

Regulate rate of administration with flow control clamp.

WARNING: Do not use flexible container in series connections.

HOW SUPPLIED

Ampicillin for Injection, USP ADD-Vantage® for intravenous injection.

Ampicillin sodium equivalent to 1 or 2 grams ampicillin per vial.

NDC 43858-123-92 1 gram ADD-Vantage® Vial, packed in 10s

NDC 43858-124-92 2 grams ADD-Vantage® Vial, packed in 10s

REFERENCES

1.

Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; Twenty-fifth Informational Supplement. CLSI document Ml00-S25. Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.

2.

Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Diffusion Susceptibility Tests; Approved Standard-Twelfth Edition. CLSI document M02-Al2, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.

3.

Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically; Approved Standard-Tenth Edition. CLSI document M07-Al0, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania 19087, USA, 2015.

Clinitest is a registered trademark of Miles, Inc.

Clinistix is a registered trademark of Bayer Corporation.

Tes-Tape is a registered trademark of Eli Lilly Company.

ADD-Vantage® is a trademark of Hospira Inc.

Manufactured in Austria by Sandoz GmbH

Rev. August 2017

1 gram Label

NCD 43858-123-15

Ampicillin for

Injection, USP

1 gram

For Intravenous Use Only

For use only with the ADD-Vantage®

diluent container.

Rx only

Single use ADD-Vantage® vial

2 grams Label

NCD 43858-124-15

Ampicillin for

Injection, USP

2 grams

For Intravenous Use Only

For use only with the ADD-Vantage®

diluent container.

Rx only

Single use ADD-Vantage® vial